Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder that significantly impacts patients' quality of life. Novel biological agents targeting the OX40 pathway have shown promise in refractory cases. We aimed to systematically evaluate the efficacy and safety of anti-OX40 therapies (amlitelimab, rocatinlimab, and telazorlimab) in moderate-to-severe AD. We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases up to January 2025 for clinical trials comparing anti-OX40 therapies with placebo in patients with AD. This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Five randomized clinical trials were included, comprising 1118 patients, of whom 857 (76.6%) received one of the anti-OX40 therapies. Both high-dose (mean difference [MD] = -17.33; 95% confidence interval [CI] = -23.79 to -10.87; P < 0.001) and low-dose (MD = -16.35; 95% CI = -27.42 to -5.28; P = 0.004) regimens significantly improved the SCORing AD, and multiple other outcomes also showed statistically significant improvements, including reductions in the mean Eczema Area and Severity Index score and body surface area affected by the disease. The incidence of any treatment-emergent adverse event was not statistically significant for either the high-dose group (risk ratio [RR] = 1.14; 95% CI = 0.82-1.59; P = 0.443) or the low-dose group (RR = 1.10; 95% CI = 0.84-1.45; P = 0.486). In conclusion, anti-OX40 therapies demonstrate clinically meaningful efficacy and an acceptable safety profile for moderate-to-severe AD, offering a potential alternative for patients with inadequate responses to current treatments. Further research is warranted to confirm these results and to refine optimal dosing strategies.